The last twenty years have witnessed the rapid advance of the application of genetic engineering techniques to increasingly complex organisms: first, single-cell microbial and eukaryotic culture systems; next, plants; and, finally, multi-cellular whole animal systems. The whole animal, as represented by various species of laboratory animals, is generally recognized as an essential tool for medical research. Laboratory animals offer a far closer approximation to the human organism than cell culture systems. Moreover, an understanding of integrative biology (e.g., the developmental and tissue-specific regulation of gene expression) can be achieved only through in vivo, whole animal studies. To this end, the laboratory mouse is presently the most widely used, available, and economical animal model used in biomedical research and, in particular, genetic engineering and transgenic-related research. In addition to the many traditional mutant mouse strains, thousands of additional strains of mice have been created in recent years through transgenic technology. This Core proposal provides a centralized AAALAC- certified resource for the production of pathogen-free transgenic (including DNA microinjection, ES cell transfer and mitochondrial transfer) mouse models. Trained professionals will provide high standards of performance, quality and timely production efficiency. For the individual projects outlined in this program project, this approach means availability of highly specialized services at reasonable costs, maximizing sponsored program dollars and investigator efforts. Furthermore, transgenic and transmitochondrial mice created by DNA microinjection, ES cell transfer, or evolving technologies will be crucial components of this program project. The specific aims of this Core will be to efficiently create genetically- engineered transgenic (including transmitochondrial and ES cell "knockout") mice for individual projects utilizing state-of-the-art technologies including: a) established DNA microinjection technology, b) established ES cell transfer procedures, and c) initiation of mitochondrial transfer techniques.